Department of Biological Sciences, NC State University, Raleigh, NC, 27695, USA.
Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA.
Mol Cell Endocrinol. 2023 Oct 1;576:112041. doi: 10.1016/j.mce.2023.112041. Epub 2023 Aug 9.
Gestational flame retardant (FR) exposure has been linked to heightened risk of neurodevelopmental disorders, but the mechanisms remain largely unknown. Historically, toxicologists have relied on traditional, inbred rodent models, yet those do not always best model human vulnerability or biological systems, especially social systems. Here we used prairie voles (Microtus ochrogaster), a monogamous and bi-parental rodent, leveraged for decades to decipher the underpinnings of social behaviors, to examine the impact of fetal FR exposure on gene targets in the mid-gestational placenta and fetal brain. We previously established gestational exposure to the commercial mixture Firemaster 550 (FM 550) impairs sociality, particularly in males. FM 550 exposure disrupted placental monoamine production, particularly serotonin, and genes required for axon guidance and cellular respiration in the fetal brains. Effects were dose and sex specific. These data provide insights on the mechanisms by which FRs impair neurodevelopment and later in life social behaviors.
妊娠期阻燃剂（FR）暴露与神经发育障碍的风险增加有关，但其中的机制在很大程度上仍不清楚。在历史上，毒理学家依赖于传统的近交系啮齿动物模型，但这些模型并不总是能最好地模拟人类的脆弱性或生物系统，尤其是社会系统。在这里，我们使用了草原田鼠（Microtus ochrogaster），一种一夫一妻制和双亲制的啮齿动物，几十年来一直被用于破译社会行为的基础，以研究胎儿 FR 暴露对中期胎盘和胎儿大脑中基因靶标的影响。我们之前已经建立了妊娠期接触商用混合物 Firemaster 550（FM 550）会损害社会性，特别是在雄性中。FM 550 暴露破坏了胎盘中单胺类物质的产生，特别是血清素，以及胎儿大脑中轴突导向和细胞呼吸所必需的基因。这些影响具有剂量和性别特异性。这些数据为 FR 损害神经发育和生命后期社会行为的机制提供了见解。
